1. β-Amidoaldehydes via oxazoline hydroformylation
David S. Laitar, John W. Kramer, Bryan T. Whiting, Emil B. Lobkovsky and Geoﬀrey W. Coates*. Chem. Commun., 2009, 5704–5706
The mechanism for hydrogenolysis of the alcohol-substituted intermediate to 3 has not been studied. In the homologation of benzyl alcohols using synthesis gas and catalytic HCo(CO)4, the major products are frequently methyl benzenes and an analogous reaction mechanism may be operative here. The tetrahydrocarbazole core found in 3 is present in a number of bioactive molecules including Ramatroban, a drug used to treat coronary artery disease and asthma, and Frovatriptan, a drug used to treat migraine headaches.
2. Hot off the Press
Robert A. Hill and Andrew Sutherland. Nat. Prod. Rep., 2012, 29, 829–833
Gotor and co-workers have reported two enzymatic approaches for the asymmetric synthesis of (R)-ramatroban, an indolepropanic acid used for the treatment of allergic rhinitis and asthma. A key alcohol intermediate, (S)-2,3,4,9-tetrahydro-1H-carbazol-3-ol was prepared by CAL-B mediated kinetic resolution or by reduction of the corresponding ketone with alcohol dehydrogenase (ADH-A) (Scheme 5). The alcohol formed from both biocatalytic routes could be easily converted to (R)-ramatroban in only four steps and in 30% global yield.
3. Total sythesis of a thromboxane receptor antagonist, terutroban
Wasim Ahmed, Prathama S. Mainkar, Srihari Pabbarajaa and Srivari Chandrasekhar*. Org. Biomol. Chem.,2015, 13,2951–2957
In one of the studies to find a selective antagonist, it was observed that compounds containing a carboxylic acid and a benzenesulfonamide group separated by a spacer were found to be the best among the compounds tested. Ramatroban (1b), a compound with these features, marketed as Baynas® by Bayer and Nippon Shinyaku Co. for allergic rhinitis, is a selective TP receptor antagonist. The pharmacophore was further explored by Lavielle et al., which led to the identification of a tetrahydronaphthalene derivative, terutroban (2) as a TP receptor antagonist.